Methylation Distribution and RNA Sequencing: Insights from Large-Scale Studies

I continued watching the ONT “Empowering comprehensive sequencing at scale” session. The next speaker in this session was Brynja Sigurpalsdottir who spoke about large-scale methylation studies. They spoke about how base calling is used to detect methylation. The team sequenced 7,179 whole blood samples sequenced on 8906 PromethION R9.4 flowcells! Twenty-two samples were sequenced on 28 R10.4 flow cells. Methylation is being called for samples. The sample-to-sample comparison revealed consistency. The team identified bimodal methylation distribution. Quality filters can be used to enhance accuracy. All this work was published in a study and a second one in Nature Genetics. The team concluded that methylation-depleted sequences (MDS) can be used on phased samples. About forty percent were associated with a sequence variant. They then phased the RNA sequences from 896 samples. All of the methylation-depleted sequences were associated with mRNA expression differences. Additionally, the identified ASM-QTLs correspond to disease-associated variants. Sigurpalsdottir concluded that “the sequence variants is the primary driver of correlations between CpG methylation and gene expression.”

Can methylation patterns and variants be used as clinical markers? AI-generated image.